Nontransformed quiescent rat kidney fibroblasts exposed to tumor promoting agents (TPA) or growth promoting hormones such as epidermal growth factor or sarcoma growth factor showed a definite increase in ornithine decarboxylase (ODC) and plasminogen activator activity. It was also found that the induction of ODC could be blocked by pretreatment of cells with retinoic acid. We showed that an alteration in the collagen metabolism of tumorigenic cells allowed them to proliferate in the presence of hydroxyproline analogues. In contrast, nontumorigenic cells failed to grow in media supplemented with cis-hydroxyproline, which is an analogue of hydroxyproline. A high degree of karyotypic heterogeneity was observed in four cell lines established from four murine tumors arising from subcutaneous implants of C3H/10T 1/2 cells attached to plastic plates. Each of these tumor cell lines possessed unique tumor associated transplantation antigens.